Association of Dapagliflozin Use With Clinical Outcomes and the Introduction of Uric Acid–Lowering Therapy and Colchicine in Patients With Heart Failure With and Without Gout
Authors: Jawad H. Butt, Kieran F. Docherty, Brian L. Claggett, Akshay S. Desai, Magnus Petersson, Anna Maria Langkilde, Rudolf A. de Boer, Adrian F. Hernandez, Silvio E. Inzucchi, Mikhail N. Kosiborod, Lars Køber, Carolyn S. P. Lam, Felipe A. Martinez, Piotr Ponikowski, Marc S. Sabatine, Sanjiv J. Shah, Muthiah Vaduganathan, Pardeep S. Jhund, Scott D. Solomon, John J. V. McMurray
Journal: JAMA Cardiology (2023)

Importance Gout is common in patients with heart failure (HF), and sodium-glucose cotransporter 2 inhibitors, a foundational treatment for HF, reduce uric acid levels. Objective To examine the reported prevalence of gout at baseline, the association between gout and clinical outcomes, and the effect of dapagliflozin in patients with and without gout and the introduction of new uric acid–lowering therapy and colchicine. Design, Setting, and Participants This post hoc analysis used data from 2 phase 3 randomized clinical trials conducted in 26 countries, DAPA-HF (left ventricular ejection fraction [LVEF] ≤40%) and DELIVER (LVEF &amp;amp;gt;40%). Patients with New York Heart Association functional class II through IV and elevated levels of N-terminal pro–B-type natriuretic peptide were eligible. Data were analyzed between September 2022 and December 2022. Intervention Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy. Main Outcomes and Measures The primary outcome was the composite of worsening HF or cardiovascular death. Results Among 11 005 patients for whom gout history was available, 1117 patients (10.1%) had a history of gout. The prevalence of gout was 10.3% (488 of 4747 patients) and 10.1% (629 of 6258 patients) in those with an LVEF up to 40% and greater than 40%, respectively. Patients with gout were more often men (897 of 1117 [80.3%]) than those without (6252 of 9888 [63.2%]). The mean (SD) age was similar between groups, 69.6 (9.8) years for patients with gout and 69.3 (10.6) years for those without. Patients with a history of gout had a higher body mass index, more comorbidity, and lower estimated glomerular filtration rate and were more often treated with a loop diuretic. The primary outcome occurred at a rate of 14.7 per 100 person-years (95% CI, 13.0-16.5) in participants with gout compared with 10.5 per 100 person-years (95% CI, 10.1-11.0) in those without (adjusted hazard ratio [HR], 1.15; 95% CI, 1.01-1.31). A history of gout was also associated with a higher risk of the other outcomes examined. Compared with placebo, dapagliflozin reduced the risk of the primary end point to the same extent in patients with (HR, 0.84; 95% CI, 0.66-1.06) and without a history of gout (HR, 0.79; 95% CI, 0.71-0.87; P = .66 for interaction). The effect of dapagliflozin use with other outcomes was consistent in participants with and without gout. Initiation of uric acid–lowering therapy (HR, 0.43; 95% CI, 0.34-0.53) and colchicine (HR, 0.54; 95% CI, 0.37-0.80) was reduced by dapagliflozin compared with placebo. Conclusions and Relevance This post hoc analysis of 2 trials found that gout was common in HF and associated with worse outcomes. The benefit of dapagliflozin was consistent in patients with and without gout. Dapagliflozin reduced the initiation of new treatments for hyperuricemia and gout. Trial Registration ClinicalTrials.gov Identifiers: NCT03036124 and NCT03619213